Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings.

Ivan P Mosiagin,Dar’Ya V Spiridonova,Sergey P Tunik,Olesya A Tomashenko,Alexander F Khlebnikov,Mikhail S Novikov

doi:10.3762/bjoc.17.105

Abstract

A wide range of derivatives with new pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline skeleton was synthesized by free-radical intramolecular cyclization of o-bromophenyl-substituted pyrrolylpyridinium salts using the (TMS)3SiH/AIBN system. The cyclization provides generally good yields of pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline hydrobromides having no additional radical-sensitive substituents. The free bases can be obtained from the synthesized hydrobromides in quantitative yield by basification at room temperature. The selectivity control of intramolecular arylation was achieved by replacing the halogen: the use of 1-(2-(ortho-bromophenyl)-4-(ortho-iodophenyl)pyrrol-3-yl)pyridinium bromide makes it possible to obtain a monocyclization product, and the bicyclization product from the dibromo derivative. The procedure is also applicable to obtain 3-arylpyrido[2,1-a]pyrrolo[3,2-c]isoquinoline derivatives including 2-unsubstituted skeletons that are inaccessible via Pd-catalyzed cyclization.

Highlights

Polycyclic heteroaromatic molecules, which have a tunable electronic structure and excellent self-assembling properties, are highly desirable in materials science, especially in post-silicon electronics [1,2,3,4]
The intramolecular free-radical cyclization is widely used for the synthesis of heteroaromatic compounds [23,24,25,26], only a few examples of the successful use of radical cyclization for the synthesis of pyrrole-containing fused heteroaromatics are known in the literature [23,24,25,26,27,28,29,30]
We initiated our study with the attempts to carry out the cyclization of 4-(2bromophenyl)pyrrole 1a under standard radical cyclization conditions (azobisisobutyronitrile (AIBN)/Bu3SnH), which previously had been successfully used for the cyclization of 2-bromophenyl-substituted pyrroles into 7-oxa-2a1azabenzo[b]-cyclopenta[pq]pleiadenes [30]

Summary

Introduction

Polycyclic heteroaromatic molecules, which have a tunable electronic structure and excellent self-assembling properties, are highly desirable in materials science, especially in post-silicon electronics [1,2,3,4]. We report an effective method for the assembly of pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline and related frameworks via a free radical cyclization of pyrrolylpyridinium salts. An attempt to use AIBN/Bu3SnH for the cyclization of pyrrole 1a to compound 3a only led to a tarring of the reaction mixture, regardless of the temperature (70–110 °C, MeCN) and the protocol for mixing the reagents (Scheme 2).

Results

Conclusion